This STTR grant is aimed to reduce pain from repeated needle pricks by improving the monitoring of glucose homeostasis (GH) in neonates by developing a real-time glucose monitoring device. The innovation utilizes a micro-needle based lab-on-a-patch platform invented by STTR partner, George Washington University (GWU). GH is usually monitored by blood test via a heel stick, or blood is sent to the lab for confirmation but variation from actual levels may be as much as 10-20 mg/dL. Infants at risk for GH may require glucose testing every three hours or 8 times/day necessitating a needle prick on the heel to obtain a blood sample and then using a bedside reagent test-strip glucose analyzers. The lack of real-time glucose monitors in neonates is a major unmet need for reducing sample volume collection and needle pricks. A bendable, stretchable microfluidic patch for real-time monitoring of glucose using interstitial fluids (or blood) in NICU infants will be th first product for reducing pain and the frequency of needle pricks to once every 24 hours. This biosensor will securely communicate with a smartphone app via Zansors mobile health IT cloud system. Proof-of-principle data by GWU was shown in Nature's Scientific Reports Jan. 2013 reporting a miniaturized lab-on-a-patch technology integrating semiconductor/CMOS sensors and electronics with microfluidics on a flexible substrate via liquid metal interconnects. Zansors' possesses an innovative telemedicine system with encryption and HIPAA compliance that can be integrated to this proposed device. Phase I Hypothesis: A bendable, stretchable sensor platform that integrates a hybrid of CMOS electrochemical sensors/electronics chip, microfluidic channels, and stretchable electrical interconnects may use less interstitial fluid sample and less needle pricks, and offer a real-time sensor that monitors GH and continuously for long terms (24 hours) unobtrusively and then send the secure wireless data to a HIPAA-compliant telemedicine mobile health cloud system. Specific Aim 1: Develop a wearable lab-on-a-patch with micro-needle. Design electrochemical glucose sensors and CMOS electronics in COTS technology; Finish the PDMS microfluidic device design and fabrication with soft lithography. Specific Aim 2: Adapt and calibrate the algorithm to compute GH from fluid data in real-time, and develop a mobile app to collect, process, analyze and store data from the device and communicate with a telemedicine and digital health cloud system. Specific Aim 3: Using glucose solutions, demonstrate a proof-of-principle packaged bendable, stretchable CMOS/Microfluidic system for glucose monitoring. The neonatal glucose monitor market is a subset of the larger continuous glucose monitoring (CGM) market. CGM is set to grow to $568 million by 2020.